Sequential chemotherapy and immunotherapy for the treatment of metastatic melanoma

Interferon (IFN) has numerous biological properties, and more recently a new role for interferon has emerged, as a modulator of cytotoxic chemotherapeutic agents. This is based upon preclinical data that demonstrate additive and/or synergistic effects of IFN with a number of anticancer drugs including cisplatin against human cancer cell lines. Therefore, we evaluated the outpatient use of recombinant alpha 2a-interferon, 3-15 MU/m2 given on 3 consecutive days, subcutaneously, followed by intravenously administered cisplatin, 25-60 mg/m2, every 21 days. In this phase I clinical study, 23 patients with advanced malignant melanoma were treated. Dose-limiting toxicities included decline in performance status, fatigue, and anorexia. No synergistic or unpredictable toxicities were seen. Of the 20 patients who completed two cycles of therapy, there were three partial responses, for an overall response rate of 15%. Interestingly, responses occurred at the intermediate dose levels.